The proposed study will examine the feasibility, acceptability, safety, effectiveness, and cost of an integrated care program for hepatitis C, addiction, and HIV prevention in active injection drug users (IDUs), in comparison with standard, separate treatment for each of these conditions. Hepatitis C is already the leading cause of liver failure and liver transplantation in the US, and the disease burden and health care costs are expected to continue to rise in coming years. IDUs constitute the core of the hepatitis C epidemic, with prevalence rates >70% in most studies. But although antiviral treatment can eradicate the infection in many patients, few studies have reported successful treatment of this infection in active illicit drug users, and they are rarely offered antiviral treatment. In collaboration with community-based organizations providing services to IDUs in the South Bronx and East Harlem, we developed a multidisciplinary, integrated-care program and found that we could effectively treat both hepatitis C and substance abuse in IDUs recruited from community-based settings who were actively using illicit drugs. The program provided primary care, hepatitis C specialty care, mental health services, and substance abuse treatment, using Case Managers and Multidisciplinary Case Conf- erences to coordinate and integrate services from multiple, geographically separate providers. By reducing illicit drug use and providing HIV risk reduction the program reduces high-risk injection and sexual HIV risk behavior as well. This model has the advantage of delivering integrated, multidisciplinary care primarily in community-based settings where drug users are comfortable receiving services. Moreover, because it integrates care from geographically separate providers it is replicable in the vast majority of settings where co- location of multidisciplinary services is not possible. NIH has identified research comparing integrated vs. separate treatment of substance abuse and comorbid conditions as high-priority Comparative Effectiveness Research. We hypothesize that for patients suffering from addiction and hepatitis C, an integrated approach to treating these conditions together will be more effective than fragmented approaches to each condition separately. The Specific Aims of this study are to assess: (1) the effectiveness of hepatitis C treatment, (2) the safety of hepatitis C treatment, (3) substance abuse treatment outcomes, and (4) reduction in HIV risk behaviors in a community-based sample of active IDUs randomized to receive integrated vs. separate care. Chronic hepatitis C is the number one cause of chronic liver disease and liver cancer in most of the Western world. An estimated one million active IDUs in the US have hepatitis C and no access to treatment. Without better models of care, many will require liver transplants or die. The hepatitis C epidemic threatens to overwhelm the fragile and fragmented healthcare infrastructure serving the indigent, precipitating a healthcare crisis of major proportions. Understanding how to engage active IDUs in treatment for substance abuse and hepatitis C will be critical to mitigating the extraordinary morbidity and mortality these epidemics will cause. PUBLIC HEALTH RELEVANCE: The purpose of the proposed study is to examine the effectiveness of integrated care program for hepatitis C, addiction, and HIV prevention in active injection drug users (IDUs), in comparison with standard, separate treatment for each of these conditions. Hepatitis C is the leading cause of liver failure and liver transplantation in the US, and the disease burden and health care costs are expected to dramatically increase in the coming decades. Successful methods for engaging active IDUs in treatment for substance abuse and hepatitis C will be critical to mitigating the extraordinary morbidity and mortality these epidemics will cause.